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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of E-series prostaglandins (PGE) on hormone-stimulated glycogenolysis was studied in isolated rat hepatocytes. As previously reported, the physiologically active analogue 16,16-dimethyl-PGE2 inhibited glucagon-stimulated glycogenolysis. This effect could be reproduced by repetitive addition of PGE2 to compensate for PGE2 catabolism. In contrast, glycogenolysis stimulated by N6,O2'-dibutyryladenosine-3',5'-cyclic monophosphate (dibutyryl-cAMP) was unaffected by either PGE2 or 16,16-dimethyl-PGE2 (rate of glycogenolysis with 0.34 microM dibutyryl-cAMP plus 1.7 microM 16,16-dimethyl-PGE2 = 99 +/- 6% of rate with 0.34 microM dibutyryl-cAMP alone; mean +/- SEM, N = 5). Similarly, glycogenolysis stimulated by 8-bromoadenosine-3',5'-cyclic monophosphate was not inhibited by PGE2 or 16,16-dimethyl-PGE2. Epinephrine-stimulated glycogenolysis was inhibited by 16,16-dimethyl-PGE2 in a dose-dependent manner. PGE inhibited the cAMP-independent stimulation of glycogenolysis resulting from phenylephrine or angiotensin II exposure (rate of glycogenolysis with 8 microM phenylephrine + 1.7 microM 16,16-dimethyl-PGE2 = 65 +/- 10% of rate with 8 microM phenylephrine alone, N = 4, P less than 0.05; 4.9 microM angiotensin II + 1.7 microM 16,16-dimethyl-PGE2 = 75 +/- 7% of rate with 4.9 microM angiotensin II alone, N = 4, P less than 0.05). Glycogenolysis stimulated by the calcium ionophore A23187 was also inhibited by PGE (rate of glycogenolysis with 0.55 micrograms/ml A23187 + 1.7 microM 16,16-dimethyl-PGE2 = 83 +/- 5% of rate with 0.55 micrograms/ml A23187 alone, N = 7, P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of E-series prostaglandins on cyclic AMP-dependent and -independent hormone-stimulated glycogenolysis in hepatocytes. 298 82

The role of calcium ion mobilization in modulation of secretion of the ovarian protein hormone relaxin by porcine luteal cells was examined by use of a reverse hemolytic plaque assay. In this assay, luteal cells were cocultured in monolayers with protein-A-coupled ovine erythrocytes. In the presence of porcine relaxin antiserum and complement, a zone of hemolysis, a plaque, developed around relaxin-releasing luteal cells. The rate of development of plaques in time-course experiments was used in this study as an index of the rate of relaxin release. Exposure of luteal cell-containing monolayers to the calcium-mobilizing agent A23187 (40 nM to 5 microM) resulted in a dose-related increase in the rate of relaxin-plaque formation. This effect [and the influence of a stimulatory secretagogue, prostaglandin E2 (PGE2; 1 microM)] was suppressed by coculture with Co2+ (5 mM), a calcium channel blocker. These results are consistent with the view that calcium ion redistribution within porcine luteal cells forms a pathway that subserves, at least in part, the rates of basal and stimulated relaxin release in vitro. However, A23187 was equally effective in enhancing the rate of plaque formation when the monolayers were bathed in a low calcium medium (mean +/- SEM, 6.61 +/- 0.92 microM Ca2+), rather than a calcium-replete medium (1.56 +/- 0.09 mM Ca2+). Likewise, neither basal nor PGE2-stimulated (1 microM) relaxin secretion was abrogated by culture of monolayers in low calcium medium. These data suggest that the stimulatory effect of A23187 (and perhaps PGE2) arose predominantly through redistribution of calcium stored within intracellular sites in luteal cells, rather than entrance of calcium into the cell from the extracellular medium. Yet, incompatible with this interpretation, we observed that TMB-8 [8-(N,N-diethylamino)octyl 3,4,5-trimethoxybenzoate hydrochloride; a putative inhibitor of intracellular calcium redistribution] enhanced rather than blocked A23187- or PGE2-stimulated relaxin release. This result is consistent with the possibility that TMB-8 mobilized (rather than blocked) calcium in this cell system or that it acted via calcium-independent mechanisms. We conclude that calcium mobilization has the potential to act as a molecular pathway that transduces secretion of an ovarian peptide hormone, relaxin. However, the exact nature and physiological role(s) of the Ca2+ pathway in the control of relaxin secretion and the interrelationships of this mechanism with other intracellular messengers that may also modulate ovarian peptide secretion remain to be more clearly defined.
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PMID:Regulation of relaxin release from monodispersed porcine luteal cells: effect of calcium ionophore A23187 and calcium channel blockers. 313 4

The dilator stimuli that contribute to postasphyxial increases in cerebral blood flow in the neonate are unclear. To assess the possible role of cyclooxygenase products in these responses, we measured pial arteriolar diameter in six piglets and determined levels of prostaglandin (PG) E2 and 6-keto-PG F1 alpha (hydrolysis product of PGI2) in cerebrospinal fluid (CSF) bathing the parietal cortex during control conditions, after 4-10 min of complete respiratory arrest (asphyxia), and after 5-12 min of reventilation. Pial arterioles are important resistance vessels in the cerebral circulation. Baseline pial arteriolar diameter was 220 +/- 40 micron (mean +/- SEM) and increased to a maximum of 252 +/- 49 and 267 +/- 56 micron after asphyxia and reventilation, respectively. During control conditions, CSF PGE2 (n = 6) and 6-keto-PGF1 alpha (n = 4) levels were 1947 +/- 310 and 794 +/- 147 pg/ml, respectively. During asphyxia, CSF levels of PGE2 did not increase, whereas 6-keto-PGF1 alpha increased modestly. During reventilation, CSF PGE2 increased to 3576 +/- 499 pg/ml, and 6-keto-PGF1 alpha increased to 2846 +/- 123 pg/ml. In other experiments, we determined that these CSF levels of PGE2 and PGI2 (as 6-keto-PGF1 alpha) were within the vasodilator range for pial arterioles. We conclude that postasphyxial increases in pial arteriolar diameter are associated with a rise in CSF levels of dilator prostanoids.
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PMID:Postasphyxial increases in prostanoids in cerebrospinal fluid of piglets. 314 95

Simultaneous determination of urinary excretion rates of primary unmetabolized prostanoids and their enzymatic metabolites were performed by gas chromatography-mass spectrometry (GC/MS) or tandem mass spectrometry (GC/MS/MS). Changes in kidney function were induced by acute (4 h) volume expansion. Despite marked changes in urine flow, GFR, urinary pH, osmolality, sodium and potassium excretion, only a insignificant or transient rise in the enzymatic prostanoid metabolites (2,3-dinor-6-keto-PGF1 alpha, PGE-M, 2,3-dinor-TxB2 and 11-dehydro-TxB2) was observed. The excretion rates of the primary prostanoids were elevated in parallel with the rise in urine flow: PGE2 rose (p less than 0.05) from 14.2 +/- 4.0 to 86.2 +/- 20.7, PGF2 alpha from 60.0 +/- 4.9 to 119.8 +/- 24.0, 6-keto-PGF2 alpha from 7.2 +/- 1.3 to 51.5 +/- 17.0, and TxB2 from 11.2 +/- 3.3 to 13.6 +/- 3.6 ng/h/1.73 m2 (means +/- SEM) at the maximal urine flow. Except for 6-keto-PGF1 alpha and TxB2, this rise in urinary prostanoid levels was only transient despite a sustained fourfold elevated urine flow. We conclude that urine flow rate acutely affect urine prostanoid excretion rates, however, over a prolonged period of time these effects are not maintained. The present data support the concept that urinary levels of primary prostanoids mainly reflect renal concentrations whereas those of enzymatic metabolites reflect systemic prostanoid activity. From the excretion pattern of TxB2 one can assume that this prostanoid represents renal as well as systemic TxA2 activity.
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PMID:Excretion of primary prostanoids and their metabolites during acute volume expansion. 316 56

The effect of piroxicam, a nonsteroidal anti-inflammatory drug, on a transplantable adenocarcinoma in Fischer rats was studied. Forty male Fischer rats were injected with 1 X 10(6) DMH-F317 adenocarcinoma cells, and after 2 weeks were assigned to be treated with piroxicam or carrier solution. The groups were as follows: Group 1, control; Group 2, 4.0 mg/kg piroxicam; Group 3, 6.0 mg/kg piroxicam; and Group 4, 8.0 mg/kg piroxicam. Thirty-nine of forty rats developed measurable tumors during this study. At the conclusion, 60% (6/10) of the rats in Group 2 were tumor free compared to 0/10 controls, 0/10 Group 3 rats, and 1/8 Group 4 rats. (P less than 0.005, chi 2). Mean tumor volumes (mm3) were calculated for each group and converted to log10. At Week 6, the mean log10 tumor volume (+/- SEM) for Group 2 was 1.5 +/- 0.6 vs 4.1 +/- 0.1 for Group 1 (P less than 0.05). The mean log10 volume for Group 3 was 3.8 +/- 0.1 (P less than 0.05 vs Group 2). The mean log10 volume for Group 4 was 3.4 +/- 0.05 and was not significantly different from that for Group 2 (P greater than 0.05). Plasma PGE2 levels for each treatment group were determined at the conclusion of the study and no statistical difference between treatment groups was found. It is concluded that piroxicam inhibits tumor growth in this model, and may have a role as a biological response modifier in cancer therapy.
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PMID:Piroxicam inhibits the growth of an adenocarcinoma isograft in Fischer rats. 316 75

We examined the effect of in vitro incubation with the oral gold compound auranofin (AF) on arachidonic acid (AA) release and metabolism by rat alveolar macrophages (AMs). AF stimulated dose- and time-dependent release of 14C-AA from prelabeled AMs, which reached 4.7 +/- 0.3% (mean +/- SEM) of incorporated radioactivity at 10 micrograms/ml for 90 min, as compared to 0.5 +/- 0.1% release following control incubation for 90 min (p less than 0.001). Similar dose- and time-dependent synthesis of thromboxane (Tx) A2 (measured as TxB2) and prostaglandin (PG) E2 was demonstrated by radioimmunoassay of medium from unlabeled cultures, reaching 18-fold and 9-fold, respectively, of the control values at 10 micrograms/ml AF for 90 min (p less than 0.001 for both). AF-induced TxB2 and PGE2 synthesis was inhibited by indomethacin as well as by pretreatment with methylprednisolone. No increase in the synthesis of immunoreactive leukotrienes (LT) B4 or C4 was noted at any dose or time of AF. High performance liquid chromatographic separation of 14C-eicosanoids synthesized by prelabeled AMs confirmed that AF induced the release of free AA and its metabolism to cyclooxygenase, but not 5-lipoxygenase, metabolites. The ability of AF to trigger macrophage AA metabolism may be relevant to the exacerbation of certain inflammatory processes which sometimes accompany gold therapy.
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PMID:The oral gold compound auranofin triggers arachidonate release and cyclooxygenase metabolism in the alveolar macrophage. 324 32

Fifty-four women presenting for second-trimester induction abortion received either Dilapan synthetic dilators or laminaria for pretreatment of the cervix before induction abortion using intra-amniotic prostaglandin (PG) F2 alpha. The two groups were similar with respect to age, parity, previous abortion, and gestational age. Neither group experienced any unusual complications. The same protocol for intraamniotic PGF2 alpha (40 mg) was used in all patients except for three with histories of asthma, in whom PGE2 vaginal suppositories (20 mg) were used as the induction agent. For the Dilapan group, an average of three devices was used, compared with an average of six in the laminaria group. The mean (+/- SEM) induction-abortion time for Dilapan patients was 10.9 +/- 1.3 hours, compared with 16.1 +/- 1.4 hours in the laminaria group, a statistically significant difference (P less than .05). When nulliparous women were examined separately, the mean times were 11.0 +/- 1.7 for Dilapan and 16.5 +/- 1.6 for laminaria, a medically relevant and statistically significant difference (P less than .05). Dilapan appears to be an effective alternative to laminaria that results in shorter induction-abortion intervals.
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PMID:Prospective comparison of Dilapan and laminaria for pretreatment of the cervix in second-trimester induction abortion. 329 81

This paper investigates acid disposal by gastric and duodenal mucosa with particular reference to the mechanisms of acid-stimulated luminal alkalinization in the duodenum. The bulk of solute flux across duodenal epithelium occurs by paracellular permeation, and passive diffusion of HCO3 via shunt pathways contributes substantially to luminal alkalinization by this tissue in vitro. Effects on epithelial permeability of two treatments which stimulate mucosal alkaline secretion (PGE2 and low luminal pH) were studied in vivo by measuring transmucosal fluxes of radiolabeled urea (mol wt 76) and inulin (mol wt approximately 5000). Rats were anesthetized and rates of alkalinization in segments of distal duodenum perfused with saline were monitored by continuous titration. PGE2 (10 microM, topically) increased alkaline secretion from 1.63 +/- 0.34 to 3.07 +/- 0.54 microeq/cm/hr (mean +/- SEM, N = 5). Luminal acid exposure (10 mM HCl for 10 min) increased alkalinization rate from 1.54 +/- 0.43 to 2.69 +/- 0.76; subsequent addition of PGE2 induced a further rise to 3.27 +/- 0.54. Recovery of inulin in the luminal perfusate following intravenous injection was less than 10% of that of urea. Topical PGE2 had little or no effect on recovery of either marker. Luminal acidification increased the rate of appearance of urea by 130 +/- 30% (P less than 0.01, N = 6); recovery of inulin rose slightly but did not achieve statistical significance compared with control. Thus stimulation of mucosal alkaline secretion by luminal PGE2 or acid are associated with differential effects on mucosal permeability.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Mechanisms of acid disposal and acid-stimulated alkaline secretion by gastroduodenal mucosa. 342 26

Whether cimetidine protects gastric mucosal cells independently of its antisecretory effect has been controversial. Some investigators postulate that, on the contrary, cimetidine decreases the integrity of gastric mucosa. Furthermore, whether cimetidine influences gastric prostaglandin (PG) synthesis is debated. Therefore, we investigated and compared with 16,16-dimethyl-PGE2 (dmPGE2) whether cimetidine protects cultured rat gastric mucosal cells from indomethacin, and tested whether cimetidine affects gastric PG production by these cells. Cell damage was assessed by chromium 51-release assay. Concentrations of indomethacin greater than 1 mmol/L caused cell damage and increased 51Cr release in a dose-dependent and time-dependent fashion. dmPGE2 significantly reduced indomethacin-induced increase of 51Cr release, whereas cimetidine at both nonantisecretory and antisecretory doses did not alter 51Cr release caused by indomethacin. The cultured cells released PGE2 and PGI2 in amounts of 215 +/-18 and 56 +/- 3 (mean +/- SEM) pg/10(5) cells in 1 hour, respectively. Nondamaging concentrations of indomethacin caused a dose-dependent inhibition of PG release from cultured cells with 50% inhibitory concentration at a dose of 10(-6) to 10(-7) mol/L. Cimetidine did not alter gastric PG production. In summary, exogenous PG protected gastric mucosal cells from indomethacin in vitro, but cimetidine did not. In conclusion, cimetidine, which fails to affect gastric PG production, does not directly influence the integrity of gastric mucosal cells.
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PMID:Effect of cimetidine on indomethacin-induced damage in cultured rat gastric mucosal cells; comparison with prostaglandin. 346 34

Release of arachidonate metabolites from isolated canine cerebral arteries into perfusing medium were estimated using radioimmunoassay (RIA) in vitro. The cerebral arteries were isolated from dogs sustained experimental subarachnoid hemorrhages (SAH) and the results were compared with that of normal canine cerebral arteries. The amount of 6-Keto-PG F1 alpha (stable metabolite of PGI2) and PGE2 released from normal cerebral arteries were 455 +/- 84 (n = 7) and 177 +/- 72 (n = 8) ng/min/g dry weight (mean +/- SEM), respectively. Among other arachidonate metabolites, TXB2 (stable metabolite of TXA2), PGF2 alpha, PGD2 were also measured, but release of these arachidonate metabolites were little compared with PGI2 or PGE2. The amount of 6-Keto-PGF1 alpha and PGE2 released from the cerebral arteries subjected to subarachnoid hemorrhage were 110 +/- 34 (n = 6), 169 +/- 40 (n = 6) ng/min/g dry weight respectively. In SAH group, release of 6-Keto-PGF1 alpha had diminished remarkably, but no remarkable quantitative change were seen among other arachidonate metabolite between normal and SAH groups. The diminution of PGI2 release in the cerebral artery subjected to SAH may be involved in the pathogenesis of cerebral vasospasm. The release of PGs from canine pial arteries induced by the exposure of the pial arteries to red blood cell hemolysate was also estimated by RIA. The release of PGE2 tended to increase following to exposure to hemolysate but no other arachidonate was increased.
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PMID:[Effects of the subarachnoid hemorrhage on the release of arachidonate metabolites from canine cerebral arteries]. 354 66


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